Two mechanisms regulating the activity of the sodium transport system of the cell membrane are to be studied. The tissue to be used is primarily the salt gland of the duck. One mechanism to be investigated is the stimulation of sodium transport by cholinergic agonists. Our studies demonstrates that the sodium pump is not activated by intracellular sodium as is widely believed, but depends on another mechanism. The mechanism appears to be a cascade system with calcium acting as a second messenger in the sequence and cyclic GMP acting as the third messenger. A feedback mechanism is proposed to explain the constant intracellular sodium levels in the salt gland secretory cells during fluid secretion. Experiments are described to test various aspects of the proposed cascade system and the integral feedback mechanism. We have also found that cholinergic activation of the pump is mediated by an identical mechanism in the rat submandibular gland. Further comparative studies between the salt gland and the submandibular gland are proposed. The second mechanism to be examined is the control of synthesis of NaK-ATPase. The glands exhibit a large increase in sodium transport capacity and NaK-ATPase activity after ducks are transferred chronically to a saline regimen. We have demonstrated that the increased activity is due to an increased enzyme synthesis and is not an activation effect. We are presently extracting a messenger RNA fraction from salt gland tissue and synthesizing proteins in a cell free system. We propose to isolate the mRNA for NaK-ATPase and determine whether the increase in NaK-ATPase synthesis is due to the presence of more mRNA in the gland. Isolated mRNA for Nak-ATPase will permit studies on the assembly of NaK-ATPase into the cell membrane. As a first step in this direction, it is proposed that the N-terminal sequence of the newly synthesized NaK-ATPase proteins be determined to find whether leader sequences are present. Experiments are also proposed to determine whether cyclic GMP is the stimulus triggering the increase in Nak-ATPase synthesis.